The interaction of trypsin with several of its protein inhibitors will be studied with UV-visible spectrophotometric techniques to determine values for many of the equilibria and rate constants involved. The temperature, pH, ionic composition and hydrostatic pressure of the reaction mixture will be varied. The use of hydrostatic pressure is apparently unique in the study of trypsin-protein inhibitor reactions. Many aspects of these reactions involve the binding of metal ions, the binding of water molecules, the release of water molecules, the formation or the breaking of a covalent bond (such as in the modified-virgin interconversion of some inhibitor molecules). All of these processes occur with significant volume changes that should make them sensitive to the hydrostatic pressure of the incubation. The results of the incubatons with hydrostatic pressure will confirm many of the proposed mechanisms because values of the volume changes can be calculated from the pressure dependence of the reactions. The interpretation of the kinetic and equilibrium data on the interaction of trypsin and its inhibitors will require the determination of the effects of pressure on the partial molal volumes of the reactants involved and on the pH of the media used. All of the facilities needed to perform this study are available in this laboratory. This study will contribute to the understanding of mechanisms in the action of proteinase inhibitor proteins. These molecules and their interactions are involved in a gamut of processes such as in the regulation of blood pressure, in blood clotting and in emphysema.